Infection with the Gram-negative bacterium Helicobacter pylori is a primary cause of human gastritis and gastric ulcer. H. pylori infection is also correlated with lymphoma of the mucosa associated lymphoid tissues (MALT) and gastric cancer. In both humans and in animal models, serum and mucosal antibody responses to Helicobacter infection can be detected. Studies in animal models imply that the antibody response to vaccination with H. pylori antigens may confer protection against Helicobacter colonization. In contrast, despite high antibody titers in infected human patients, clearance of H. pylori from the human digestive tract has rarely if even been observed, suggesting that antibodies induced by infection are not protective. Further, it has been postulated that host antibody responses to H. pylori may contribute to disease pathology through autoimmune and inflammatory processes. Clinical studies suggest that the antibody response to H. pylori evolves during the course of bacterial infection, colonization and persistence. We hypothesize that the antibody repertoire induced by immunization differs from that induced by infection with live H. pylori bacteria. Furthermore, we speculate that identification of the antigen- and isotype-specificity of these responses will inspire improved strategies for vaccine-induced protection of humans from H. pylori disease. Therefore, we will apply phage-display methodology to capture the expressed antibody repertoire and monoclonally analyze the temporal progression and antigenic- specificities of the mucosal and systemic antibodies resulting from infection. Our first aim will be to establish conditions for colonization of mice by H. pylori and demonstrate protection conferred by immunization with H. pylori lysates. From the test population, our second aim will be to capture permanent genetic records of the humoral response of mice to infection by the construction of phage-display libraries of the antibody repertoire. Finally our third aim will be to examine the phage-display libraries for the isotype characteristics of antibodies directed against Helicobacter and self antigens, and to use these antibodies to identify antigens involved in disease pathology. The recombinant antibody approach to this problem, may prove generally useful for the study of the immune response to a variety of infectious organisms and disease states.